A specific decrease in synthetic activity of the L-arginine-NO metabolic pathway contributes to decreased endothelium-dependent vasodilation in patients with congestive heart failure.

Congestive heart failure (CHF) is a common cardiovascular disorder that is characterised, in part, by a decreased cardiac output reserve. Accordingly, there is ongoing interest in the role of positive inotropic agents (e.g. adrenergic agonists and phosphodiesterase type III inhibitors, which mediate their cardiovascular effects via a cyclic adenosine monophosphate-dependent mechanism) in the treatment of CHF. However, enthusiasm for positive inotropic therapy in CHF has been dampened by the results of clinical trials, which have shown that these drugs are associated with an increased risk of mortality. Calcium sensitising agents are a heterogeneous group of positive inotropic agents that mediate their cardiovascular actions (at least in part) by increasing the sensitivity of the contractile elements to calcium. Increased sensitivity to calcium may be related to changes in calcium binding to troponin C, or to direct effects on the actin-myosin complex. In addition, the inhibition of phosphodiesterase type III may contribute to the positive inotropic action of calcium sensitising agents. Five agents with calcium sensitising properties (pimobendan, levosimendan, MCI-154, EMD-53998 and CGP-48506) have been studied as possible therapies for CHF. All of these agents have demonstrated a positive inotropic action in isolated cardiac tissue and in animal models of CHF. In clinical trials, pimobendan, the most extensively studied of these drugs, was well tolerated and was associated with improved exercise tolerance during the first 6 months of therapy; however, it was also associated with a nonsignificant trend towards increased mortality. Because many of the calcium sensitising agents also inhibit phosphodiesterase type III activity, the long term safety of these agents is uncertain. Large-scale survival trials are required to determine the long term safety and efficacy of these agents before their role in the treatment of CHF can be defined.

Brain sag is a rare but serious postoperative complication after craniotomy. It is a clinical entity that refers to severe cerebrospinal fluid hypovolemia causing acute neurologic decompensation and obtundation. The established treatment is trendelenberg positioning. We present 3 cases of severe brain sag in which patients developed acute neurologic deterioration unresponsive to conventional treatment. An epidural blood patch was performed emergently to prevent further neurologic decline. The administration of epidural blood patch resulted in immediate and dramatic reversal of obtundation in each of these patients. Epidural blood patch may be a life-saving intervention in postcraniotomy patients presenting with refractory brain sag. It should be offered in patients who meet the criteria for brain sag and are unresponsive to conventional treatment modalities, despite the clinical presentation of herniation and coma.

This is a prospective pilot study looking at the utility of Transcutaneous Electrical Nerve Stimulator (TENS) trial as a screening tool prior to spinal cord stimulator (SCS) implant to identify patients who may fail a SCS trial. The accepted screening test prior to a permanent SCS implant is a SCS trial. Patients may fail the SCS trial due to several causes of which one is the inability to tolerate stimulation induced paresthesias. Twenty five patients scheduled for a SCS trial for the treatment of refractory pain secondary to Failed Back surgery syndrome underwent a TENS trial and psychological evaluation by personnel uninvolved in the SCS trial. Data was collected by personnel not involved in the SCS trial or permanent placement. Twenty patients completed the study. Data collected included area of coverage, paresthesia tolerance, pain and anxiety measured on a VAS scale. Comparability between the groups were analyzed using Pearson's correlation, Fisher Exact test and simple regression analysis. We noted a significant correlation between ability to tolerate TENS and SCS induced paresthesias. Statistically significant correlation was also noted between pre SCS trial anxiety score and high pain score during SCS trial. We conclude that there is potential applicability of a TENS trial as a non invasive screening tool which may promote cost effectiveness and decrease unnecessary procedural risks to the patient by avoiding SCS trial in select patients.

Summary Antibody‐Mediated Rejection (AMR) due to donor‐specific antibodies (DSA) is associated with poor outcomes after lung transplantation. Currently, there are no guidelines regarding the selection of treatment protocols. We studied how DSA characteristics including titers, C1q, and mean fluorescence intensity (MFI) values in undiluted and diluted sera may predict a response to therapeutic plasma exchange (TPE) and inform patient prognosis after treatment. Among 357 patients consecutively transplanted without detectable pre‐existing DSAs between 01/01/16 and 12/31/18, 10 patients were treated with a standardized protocol of five TPE sessions with IVIG. Based on DSA characteristics after treatment, all patients were divided into three groups as responders, partial responders, and nonresponders. Kaplan–Meier Survival analyses showed a statistically significant difference in patient survival between those groups (P = 0.0104). Statistical analyses showed that MFI in pre‐TPE 1:16 diluted sera was predictive of a response to standardized protocol (R2 = 0.9182) and patient survival (P = 0.0098). Patients predicted to be nonresponders who underwent treatment with a more aggressive protocol of eight TPE sessions with IVIG and bortezomib showed improvements in treatment response (P = 0.0074) and patient survival (P = 0.0253). Dilutions may guide clinicians as to which patients would be expected to respond to a standards protocol or require more aggressive treatment.